Experimental and clinical observations have supported the concept that the hypothalamus plays a key role in the regulation of adenohypophysial corticotropic cells secretory functions. Over 25 years ago, Guillemin, Rosenberg and Saffran and Schally independently demonstrated the presence of factors in hypothalamus which would increase the rate of ACTH secretion by the pituitary gland incubated in vitro or maintained in an organ culture. None of the secretagogs characterized met the criteria expected of a physiologic corticotropin releasing factor (CRF) until ovine CRF (oCRF) was characterized in 1981 as disclosed in U.S. Pat. No. 4,415,558, the disclosure of which is incorporated herein by reference. oCRF lowers blood pressure in mammals and stimulates the secretion of ACTH and .beta.-endorphin.
Rat CRF(rCRF) has been isolated, purified and characterized as a homologous hentetracontapeptide as disclosed in U.S. Pat. No. 4,489,163, the disclosure of which is incorporated herein by reference. The formula of human CRF has now been determined to be the same as that of rCRF, and the terms rCRF and hCRF are used interchangeably. Synthetic rCRF and oCRF stimulate ACTH and .beta.-endorphin-like activities (.beta.-END-LI) in vitro and in vivo and substantially lower blood pressure when injected peripherally, e.g. intravenously.